Dovitinib (TKI-258)

Dovitinib (TKI258, CHIR258) is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGF-1R and HER2 in cell-free assays. Phase 4.

CAS No. 405169-16-6

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 37000	国内在庫あり
10mg	JPY 25500	国内在庫あり
25mg	JPY 40500	国内在庫あり
50mg	JPY 70500	国内在庫あり
1g	JPY 298500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

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製品安全説明書

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Dovitinib (TKI-258)関連製品

関連ターゲット	FLT3-WT FLT3-ITD FLT3-D835Y	もっと見る
関連製品	Gilteritinib (ASP2215) Dovitinib (TKI258) Lactate monohydrate Tandutinib (MLN518) KW-2449 ENMD-2076 UNC2025 AST-487 (NVP-AST487) TCS 359 G-749 SKLB4771 (FLT3-IN-1) AMG 925	もっと見る
関連化合物ライブラリー	Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Angiogenesis Related compound Library HIF-1 Signaling Pathway Compound Library FDA-approved Anticancer Drug Library	もっと見る

シグナル伝達経路

FLT3シグナル伝達経路

FLT3阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
Hep3B	Growth Inhibition Assay	0.1-10 μM	24 h	induces G2 arrest	24238094
HeLa	Growth Inhibition Assay	0.1-10 μM	24 h	induces G2/M arrest in a concentration-dependent manner	24238094
C666-1	Growth Inhibition Assay	0.1-10 μM	48 h	induces G2/M delay in a concentration-dependent manner	24238094
CNE2	Growth Inhibition Assay	0.1-10 μM	48 h	induces G2/M delay in a concentration-dependent manner	24238094
HNE1	Growth Inhibition Assay	0.1-10 μM	48 h	induces G2/M delay in a concentration-dependent manner	24238094
HONE1	Growth Inhibition Assay	0.1-10 μM	48 h	induces G2/M delay in a concentration-dependent manner	24238094
RT4	Cell Viability Assay	1-10 μM	72 h	inhibits cell growth in a dose dependent manner	24325461
TCC-SUP	Cell Viability Assay	1-10 μM	72 h	inhibits cell growth in a dose dependent manner	24325461
BFTC905	Cell Viability Assay	1-10 μM	72 h	inhibits cell growth in a dose dependent manner	24325461
T24	Cell Viability Assay	1-10 μM	72 h	inhibits cell growth in a dose dependent manner	24325461
RT112	Cell Viability Assay	1-10 μM	72 h	inhibits cell growth in a dose dependent manner	24325461
HT1376	Cell Viability Assay	1-10 μM	72 h	inhibits cell growth in a dose dependent manner	24325461
MGHU4	Cell Viability Assay	1-10 μM	72 h	inhibits cell growth in a dose dependent manner	24325461
HU456	Cell Viability Assay	1-10 μM	72 h	inhibits cell growth in a dose dependent manner	24325461
5637	Cell Viability Assay	1-10 μM	72 h	inhibits cell growth in a dose dependent manner	24325461
UMC3	Cell Viability Assay	1-10 μM	72 h	inhibits cell growth in a dose dependent manner	24325461
MFE-296	Function Assay	0.05/0.1/0.5 μM	72 h	causes a decrease in STAT3, ERK, and AKT phosphorylation	24495750
AN3CA	Function Assay	0.05/0.1/0.5 μM	72 h	causes a decrease in STAT3, ERK, and AKT phosphorylation	24495750
HEC-1A	Function Assay	0.05/0.1/0.5 μM	72 h	causes a decrease in STAT3, ERK, and AKT phosphorylation	24495750
SEM-K2	Apoptosis Assay	0.1/1 μM	24 h	induces early apoptosis of SEM-K2 cells at 0.1 μM after 24 h	25202072
Nalm-6	Apoptosis Assay	2 μM	24/48 h	induces apoptosis resulting in about 72% of cell death after 24 h treatment and 81% after 48 h	25202072
HUVEC	Cell Viability Assay	0-25 μM	72 h	inhibits cell growth in a dose dependent manner	23228017
HMVEC	Cell Viability Assay	0-25 μM	72 h	inhibits cell growth in a dose dependent manner	23228017
MHCC-97H	Cell Viability Assay	0-25 μM	72 h	inhibits cell growth in a dose dependent manner	23228017
SMMC7721	Cell Viability Assay	0-25 μM	72 h	inhibits cell growth in a dose dependent manner	23228017
Huh-7	Apoptosis Assay	0-12.5 μM	24 h	sensitizes HCC cells to TRAIL- and tigatuzumab-induced apoptosis in a dose-dependent manner	22230479
Sk-Hep1	Apoptosis Assay	0-12.5 μM	24 h	sensitizes HCC cells to TRAIL- and tigatuzumab-induced apoptosis in a dose-dependent manner	22230479
Hep3B	Apoptosis Assay	0-12.5 μM	24 h	sensitizes HCC cells to TRAIL- and tigatuzumab-induced apoptosis in a dose-dependent manner	22230479
PLC5	Apoptosis Assay	0-12.5 μM	24 h	sensitizes HCC cells to TRAIL- and tigatuzumab-induced apoptosis in a dose-dependent manner	22230479
PLC5	Cell Viability Assay	0-15 μM	72 h	reduces cell viability in a dose-dependent manner	22180308
Hep3B	Cell Viability Assay	0-15 μM	72 h	reduces cell viability in a dose-dependent manner	22180308
Sk-Hep1	Cell Viability Assay	0-15 μM	72 h	reduces cell viability in a dose-dependent manner	22180308
Huh-7	Cell Viability Assay	0-15 μM	72 h	reduces cell viability in a dose-dependent manner	22180308
PLC5	Apoptosis Assay	0-15 μM	24 h	increases apoptotic cell death in a dose-dependent manner	22180308
Hep3B	Apoptosis Assay	0-15 μM	24 h	increases apoptotic cell death in a dose-dependent manner	22180308
Sk-Hep1	Apoptosis Assay	0-15 μM	24 h	increases apoptotic cell death in a dose-dependent manner	22180308
Huh-7	Apoptosis Assay	0-15 μM	24 h	increases apoptotic cell death in a dose-dependent manner	22180308
PLC5	Function Assay	0-10 μM	24 h	causes dose-dependent DNA fragmentation	22180308
Hep3B	Function Assay	0-10 μM	24 h	causes dose-dependent DNA fragmentation	22180308
Sk-Hep1	Function Assay	0-10 μM	24 h	causes dose-dependent DNA fragmentation	22180308
Huh-7	Function Assay	0-10 μM	24 h	causes dose-dependent DNA fragmentation	22180308
RT112	Function Assay	500 nM	24 h	increases the proportion of cells in G1 accompanied by a decrease in S and G2/M phases	21119661
RT4	Function Assay	500 nM	24 h	increases the proportion of cells in G1 accompanied by a decrease in S and G2/M phases	21119661
MGH-U3	Function Assay	500 nM	24 h	increases the proportion of cells in G1 accompanied by a decrease in S and G2/M phases	21119661
SW780	Function Assay	500 nM	24 h	increases the proportion of cells in G1 accompanied by a decrease in S and G2/M phases	21119661
97-7	Function Assay	500 nM	24 h	increases the proportion of cells in G1 accompanied by a decrease in S and G2/M phases	21119661
J807C	Cell Viability Assay	0-400 nM	48 h	inhibits cell growth in a dose dependent manner	15598814
Y373C	Cell Viability Assay	0-400 nM	48 h	inhibits cell growth in a dose dependent manner	15598814
K650E	Cell Viability Assay	0-400 nM	48 h	inhibits cell growth in a dose dependent manner	15598814
G384D	Cell Viability Assay	0-400 nM	48 h	inhibits cell growth in a dose dependent manner	15598814
F384L	Cell Viability Assay	0-400 nM	48 h	inhibits cell growth in a dose dependent manner	15598814
NCI-H1703	Function assay	10 uM	24 hrs	Inhibition of TNIK in human NCI-H1703 cells transfected with lentiviral vector 7TFP assessed as reduction of GSK3 inhibitor X activated TNIK-mediated Wnt/TCF/beta-catenin-dependent transcription at 10 uM after 24 hrs by luciferase reporter assay	ChEMBL
LoVo	Cytotoxicity assay	10 uM	72 hrs	Cytotoxicity against Wnt/beta-catenin signalling dependent human LoVo cells assessed as cell viability at 10 uM after 72 hrs by ATPlite assay	ChEMBL
HCT116	Cytotoxicity assay	10 uM	72 hrs	Cytotoxicity against Wnt/beta-catenin signalling dependent human HCT116 cells assessed as cell viability at 10 uM after 72 hrs by ATPlite assay	ChEMBL
Huh7	Growth Inhibition Assay		72 h	IC50=3.980 ± 0.803 μM	23546591
PLC/PRF5	Growth Inhibition Assay		72 h	IC50=3.110 ± 0.337 μM	23546591
Hep3B	Growth Inhibition Assay		72 h	IC50=0.892 ± 0.044 μM	23546591
HepG2	Growth Inhibition Assay		72 h	IC50=1.200 ± 0.226 μM	23546591
Huh7	Growth Inhibition Assay		48 h	IC50=15.007 ± 7.334 μM	23546591
PLC/PRF5	Growth Inhibition Assay		48 h	IC50=16.120 ± 4.001 μM	23546591
Hep3B	Growth Inhibition Assay		48 h	IC50=4.223 ± 0.839 μM	23546591
HepG2	Growth Inhibition Assay		48 h	IC50=2.727 ± 0.429 μM	23546591
SW780	Growth Inhibition Assay		5 d	IC50=50 nM	21119661
RT112	Growth Inhibition Assay		5 d	IC50=15 nM	21119661
RT4	Growth Inhibition Assay		5 d	IC50=5 nM	21119661
JMSU1	Growth Inhibition Assay		5 d	IC50=50 nM	21119661
J82	Growth Inhibition Assay		5 d	IC50=1400 nM	21119661
97-7	Growth Inhibition Assay		5 d	IC50=1000 nM	21119661
KMS11	Growth Inhibition Assay		72 h	IC50=90 nM	15598814
KMS18	Growth Inhibition Assay		72 h	IC50=550 nM	15598814
OPM2	Growth Inhibition Assay		72 h	IC50=90 nM	15598814
H929	Growth Inhibition Assay		72 h	IC50> 2500 nM	15598814
8226	Growth Inhibition Assay		72 h	IC50> 2500 nM	15598814
U266	Growth Inhibition Assay		72 h	IC50> 2500 nM	15598814
insect cells	Function assay		1 to 4 hrs	Inhibition of recombinant PDGFRbeta (unknown origin) expressed in baculovirus infected insect cells using biotinylated peptide substrate GGLFDDPSYVNVQNL in presence of ATP incubated for 1 to 4 hrs by time resolved fluorescence assay, IC50=0.001μM	27914362
Sf9	Function assay		1 to 4 hrs	Inhibition of recombinant human N-terminal GST/His6-tagged c-KIT (544 to 976 residues) expressed in baculovirus infected sf9 cells using biotinylated peptide substrate GGLFDDPSYVNVQNL in presence of ATP incubated for 1 to 4 hrs by time resolved fluorescen, IC50=0.001μM	27914362
Sf9	Function assay		1 to 4 hrs	Inhibition of recombinant human N-terminal GST/His6-tagged FLT3 (571 to 993 residues) expressed in baculovirus infected sf9 cells using biotinylated peptide substrate GGLFDDPSYVNVQNL in presence of ATP incubated for 1 to 4 hrs by time resolved fluorescenc, IC50=0.001μM	27914362
insect cells	Function assay		1 to 4 hrs	Inhibition of recombinant FGFR1 (unknown origin) expressed in baculovirus infected insect cells using biotinylated peptide substrate GGGGQDGKDYIVLPI in presence of ATP incubated for 1 to 4 hrs by time resolved fluorescence assay, IC50=0.008μM	27914362
insect cells	Function assay		1 to 4 hrs	Inhibition of recombinant VEGFR3 (unknown origin) expressed in baculovirus infected insect cells using biotinylated peptide substrate GGGGQDGKDYIVLPI in presence of ATP incubated for 1 to 4 hrs by time resolved fluorescence assay, IC50=0.008μM	27914362
insect cells	Function assay		1 to 4 hrs	Inhibition of recombinant VEGFR1 (unknown origin) expressed in baculovirus infected insect cells using biotinylated peptide substrate GGGGQDGKDYIVLPI in presence of ATP incubated for 1 to 4 hrs by time resolved fluorescence assay, IC50=0.01μM	27914362
insect cells	Function assay		1 to 4 hrs	Inhibition of recombinant VEGFR2 (unknown origin) expressed in baculovirus infected insect cells using biotinylated peptide substrate GGGGQDGKDYIVLPI in presence of ATP incubated for 1 to 4 hrs by time resolved fluorescence assay, IC50=0.013μM	27914362
insect cells	Function assay		1 to 4 hrs	Inhibition of recombinant FGFR1 (unknown origin) expressed in baculovirus infected insect cells using GGGGQDGKDYIVLPI as substrate after 1 to 4 hrs by time-resolved fluorescence assay, IC50=0.008μM	30503938
MFE319	Growth Inhibition Assay			IC50=1.87 ± 0.45 μM	23443805
EN	Growth Inhibition Assay			IC50=1.66 ± 0.01 μM	23443805
USPC2	Growth Inhibition Assay			IC50=1.62 ± 0.01 μM	23443805
SNGM	Growth Inhibition Assay			IC50=1.42 ± 0.13 μM	23443805
KLE	Growth Inhibition Assay			IC50=1.37 ± 0.02 μM	23443805
HEC1A	Growth Inhibition Assay			IC50=1.34 ± 0.30 μM	23443805
ISHIKAWA	Growth Inhibition Assay			IC50=1.30 ± 0.11 μM	23443805
SNGII	Growth Inhibition Assay			IC50=1.24 ± 0.28 μM	23443805
EN1	Growth Inhibition Assay			IC50=1.02 ± 0.25 μM	23443805
RL952	Growth Inhibition Assay			IC50=0.93 ± 0.01 μM	23443805
SPAC1S	Growth Inhibition Assay			IC50=0.77 ± 0.08 μM	23443805
MFE296	Growth Inhibition Assay			IC50=0.66 ± 0.19 μM	23443805
HEC155	Growth Inhibition Assay			IC50=0.66 ± 0.09 μM	23443805
AN3CA	Growth Inhibition Assay			IC50=0.50 ± 0.10 μM	23443805
MFE280	Growth Inhibition Assay			IC50=0.42 ± 0.06 μM	23443805
LS174T	Growth Inhibition Assay			IC50=4.330.47 μM	24495750
CaCO2	Growth Inhibition Assay			IC50=3.230.64 μM	24495750
SW-480	Growth Inhibition Assay			IC50=4.330.47 μM	24495750
HT-29	Growth Inhibition Assay			IC50=5.21.93 μM	24495750
HCT-116	Growth Inhibition Assay			IC50=3.050.58 μM	24495750
RS4:11	Growth Inhibition Assay			IC50=2.81 μM	25202072
HB-1119	Growth Inhibition Assay			IC50=0.028 μM	25202072
SEM-K2	Growth Inhibition Assay			IC50=0.022 μM	25202072
Nalm-6	Growth Inhibition Assay			IC50=0.382 μM	25202072
CEM/C2	Growth Inhibition Assay			IC50=1.125 μM	25202072
CCRF-CEM	Growth Inhibition Assay			IC50=0.398 μM	25202072
BaF3-p210Bcr-Abl-T315I	Growth Inhibition Assay			IC50=2.626 μM	25202073
BaF3-p210Bcr-Abl	Growth Inhibition Assay			IC50=0.692 μM	25202073
BaF3-pSRα	Growth Inhibition Assay			IC50=0.668 μM	25202073
SupB15-R	Growth Inhibition Assay			IC50=0.558 μM	25202073
SupB15	Growth Inhibition Assay			IC50=0.449 μM	25202073
EFE184	Growth Inhibition Assay			IC50=2.04 ± 0.13 μM	23443805
ECC1	Growth Inhibition Assay			IC50=2.07 ± 0.01 μM	23443805
HEC1B	Growth Inhibition Assay			IC50=2.57 ± 0.23 μM	23443805
USPC1	Growth Inhibition Assay			IC50=2.60 ± 0.13 μM	23443805
SPAC1L	Growth Inhibition Assay			IC50=3.06 ± 1.14 μM	23443805
KM12L4A	Function assay			Inhibition of VEGFR2 phosphorylation expressed in human KM12L4A cells by Western blot analysis, EC50=0.046μM	19113866
KM12L4A	Function assay			Inhibition of PDGFRbeta phosphorylation expressed in human KM12L4A cells Western blot analysis, EC50=0.051μM	19113866
KM12L4A	Function assay			Inhibition of FGFR1 phosphorylation expressed in human KM12L4A cells by Western blot analysis, EC50=0.166μM	19113866
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
U-2 OS	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
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生物活性

製品説明

Dovitinib (TKI258, CHIR258) is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGF-1R and HER2 in cell-free assays. Phase 4.

Targets

FLT3 ^[1] (Cell-free assay)	c-Kit ^[1] (Cell-free assay)	FGFR1 ^[1] (Cell-free assay)	VEGFR3/FLT4 ^[1] (Cell-free assay)	FGFR3 ^[1] (Cell-free assay)	もっとクリックする
1 nM	2 nM	8 nM	8 nM	9 nM	もっとクリックする

In Vitro
In vitro	Dovitinib potently inhibits the FGF-stimulated growth of WT and F384L-FGFR3-expressing B9 cells with IC50 of 25 nM. In addition, Dovitinib inhibits proliferation of B9 cells expressing each of the various activated mutants of FGFR3. Interestingly, there are minimal observed differences in the sensitivity of the different FGFR3 mutations to Dovitinib, with the IC50 ranging from 70 to 90 nM for each of the various mutations. IL-6-dependent B9 cells containing vector only (B9-MINV cells are resistant to the inhibitory activity of Dovitinib at concentrations up to 1 μM. Dovitinib inhibits cell proliferation of KMS11 (FGFR3-Y373C), OPM2 (FGFR3-K650E), and KMS18 (FGFR3-G384D) cells with IC50 of 90 nM (KMS11 and OPM2) and 550 nM, respectively. Dovitinib inhibits FGF-mediated ERK1/2 phosphorylation and induces cytotoxicity in FGFR3-expressing primary MM cells. BMSCs does confer a modest degree of resistance with 44.6% growth inhibition for cells treated with 500 nM Dovitinib and cultured on stroma compared with 71.6% growth inhibition for cells grown without BMSCs. Dovitinib inhibits proliferation of M-NFS-60, an M-CSF growth-driven mouse myeloblastic cell line with a median effective concentration (EC50) of 220 nM. ^[1] Treatment of SK-HEP1 cells with Dovitinib results in a dose-dependent reduction in cell number and G2/M phase arrest with reduction in the G0/G1 and S phases, inhibition of anchorage-independent growth and blockage of bFGF-induced cell motility. The IC50 for Dovitinib in SK-HEP1 cells is approximately 1.7 μM. Dovitinib also significantly reduces the basal phosphorylation levels of FGFR-1, FGFR substrate 2α (FRS2-α) and ERK1/2 but not Akt in both SK-HEP1 and 21-0208 cells. In 21-0208 HCC cells, Dovitinib significantly inhibits bFGF-induced phosphorylation of FGFR-1, FRS2-α, ERK1/2 but not Akt. ^[2]
Kinase Assay	In vitro kinase assays
Kinase Assay	The inhibitory concentration of 50% (IC50) values for the inhibition of RTKs by Dovitinib are determined in a time-resolved fluorescence (TRF) or radioactive format, measuring the inhibition by Dovitinib of phosphate transfer to a substrate by the respective enzyme. The kinase domains of FGFR3, FGFR1, PDGFRβ, and VEGFR1-3 are assayed in 50 mM HEPES (N-2-hydroxyethylpiperazine-N^′-2-ethanesulfonic acid), pH 7.0, 2 mM MgCl₂, 10 mM MnCl₂ 1 mM NaF, 1 mM dithiothreitol (DTT), 1 mg/mL bovine serum albumin (BSA), 0.25 μM biotinylated peptide substrate (GGGGQDGKDYIVLPI), and 1 to 30 μM adenosine triphosphate (ATP) depending on the K_m for the respective enzyme. ATP concentrations are at or just below K_m. For c-KIT and FLT3 reactions the pH is raised to 7.5 with 0.2 to 8 μM ATP in the presence of 0.25 to 1 μM biotinylated peptide substrate (GGLFDDPSYVNVQNL). Reactions are incubated at room temperature for 1 to 4 hours and the phosphorylated peptide captured on streptavidin-coated microtiter plates containing stop reaction buffer (25 mM EDTA [ethylenediaminetetraacetic acid], 50 mM HEPES, pH 7.5). Phosphorylated peptide is measured with the DELFIA TRF system using a Europium-labeled antiphosphotyrosine antibody PT66. The concentration of Dovitinib for IC50 is calculated using nonlinear regression with XL-Fit data analysis software version 4.1 (IDBS). Inhibition of colony-stimulating factor-1 receptor (CSF-1R), PDGFRα, insulin receptor (InsR), and insulin-like growth factor receptor 1 (IGFR1) kinase activity is determined at ATP concentrations close the K_m for ATP.
細胞実験	細胞株	B9 cells, MM cell lines
	濃度	100 nM
	反応時間	48-96 hours
	実験の流れ	Cell viability is assessed by 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium (MTT) dye absorbance. Cells are seeded in 96-well plates at a density of 5 × 10³ (B9 cells) or 2 × 10⁴ (MM cell lines) cells per well. Cells are incubated with 30 ng/mL aFGF and 100 μg/mL heparin or 1% IL-6 where indicated and increasing concentrations of Dovitinib. For each concentration of Dovitinib, 10 μL aliquots of drug or DMSO diluted in culture medium is added. For drug combination studies, cells are incubated with 0.5 μM dexamethasone, 100 nM Dovitinib, or both simultaneously where indicated. To evaluate the effect of Dovitinib on growth of MM cells adherent to BMSCs, 10⁴ KMS11 cells are cultured on BMSC-coated 96-well plates in the presence or absence of Dovitinib. Plates are incubated for 48 to 96 hours. For assessment of macrophage colony-stimulating factor (M-CSF)-mediated growth, 5 × 10³ M-NFS-60 cells/well are incubated with serial dilutions of Dovitinib with 10 ng/mL M-CSF and without granulocyte-macrophage colony-stimulating factor (GM-CSF). After 72 hours cell viability is determined using Cell Titer-Glo Assay. Each experimental condition is performed in triplicate.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	p-STAT3 / STAT3 / Mcl-1 / LC3 / Beclin 1 / p62 p-VEGFR-2 / VEGFR-2 / p-FGFR-1 / FGFR-1 p-PDGFR-β / PDGFR-β / p-ERK / ERK CDK1 / p-CDK1 / p53 / p21		31485222
	Growth inhibition assay	Cell viability		28467797

In Vivo
In Vivo	Dovitinib induces both cytostatic and cytotoxic responses in vivo resulting in regression of FGFR3-expressing tumors.^[1] Dovitinib shows a dose- and exposure-dependent inhibition of target receptor tyrosine kinases (RTKs) expressed in tumor xenografts. Dovitinib potently inhibits tumor growth of six HCC lines. Inhibition of angiogenesis correlated with inactivation of FGFR/PDGFRβ/VEGFR2 signaling pathways. In an orthotopic model, Dovitinib potently inhibits primary tumor growth and lung metastasis and significantly prolonged mouse survival. ^[2] Administration of Dovitinib results in significant tumor growth inhibition and tumor regressions, including large, established tumors (500-1,000 mm³). ^[3]
動物実験	動物モデル	8-week-old female BNX mice bearing KMS11 cells
	投与量	10, 30, or 60 mg/kg
	投与経路	Gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT05571969	Recruiting	Advanced Solid Tumors	Allarity Therapeutics\|Amarex Clinical Research	February 20 2023	Phase 1
NCT02268435	Withdrawn	Gastrointestinal Stromal Tumors	Asan Medical Center	March 2015	Phase 1
NCT01700270	Completed	Advanced Solid Tumors Excluding Breast Cancer	Novartis Pharmaceuticals\|Novartis	May 2013	Phase 1
NCT01680796	Withdrawn	Multiple Myeloma	University of Florida\|Novartis Pharmaceuticals	February 2013	Phase 1
NCT01266070	Terminated	Von Hippel-Lindau Syndrome	M.D. Anderson Cancer Center\|Novartis	November 2012	Phase 2

参考
[1] Trudel S, et al. Blood. 2005, 105(7), 2941-2948. [2] Huynh H, et al. J Hepatol. 2012, 56(3), 595-601. [3] Lee SH, et al. Clin Cancer Res. 2005, 11(10), 3633-3641. [4] Azab AK, et al. Clin Cancer Res, 2011, 17(13), 4389-4399. [5] Trudel S, et al. Blood, 2005, 105(7), 2941-2948. + 展開

参考

+ 展開

化学情報

分子量	392.43	化学式	C₂₁H₂₁FN₆O
CAS No.	405169-16-6	SDF	Download Dovitinib (TKI-258) SDFをダウンロードする
Smiles	CN1CCN(CC1)C2=CC3=C(C=C2)N=C(N3)C4=C(C5=C(C=CC=C5F)NC4=O)N
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 30 mg/mL ( (76.44 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):